Objectives Primate embryonic stem cell (ES) lines provide an in vitro model for human development. Elucidating the mechanisms controlling the differentiation of specific cell types will ultimately allow the growth of human cells in vitro that can be used to treat specific human diseases by transplantation. During 1995, we continued to characterize rhesus and marmoset ES cells, studied their development to neural and trophoblast derivatives, and began to develop ways to manipulate these cells to understand the genetic controls of cellular differentiation. We demonstrated the differentiation of rhesus ES cells to neurons in vitro, and found that retinoic acid dramatically increases the differentiation of neural derivatives. We also demonstrated the differentiation of rhesus and marmoset ES cells to trophoblast, a component of the placenta, and found that the secretion of chorionic gonadotropin by ES cell-derived trophoblast is highly responsive to gonadotropin-releasing hormone (GnRH). These findings provide new in vitro models for the study of neural and placental development, which will provide insights into the pathogenesis of human neural and reproductive diseases, two areas poorly represented by rodents models. Key words non-surgical embryo recovery, blastocyst, embryonic stem cells, primate.